Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population

• Published in: Scientific reports Vol. 10; no. 1; pp. 13706 - 11
• Main Authors: Romero-Hidalgo, Sandra, Flores-Rivera, José, Rivas-Alonso, Verónica, Barquera, Rodrigo, Villarreal-Molina, María Teresa, Antuna-Puente, Bárbara, Macias-Kauffer, Luis Rodrigo, Villalobos-Comparán, Marisela, Ortiz-Maldonado, Jair, Yu, Neng, Lebedeva, Tatiana V., Alosco, Sharon M., García-Rodríguez, Juan Daniel, González-Torres, Carolina, Rosas-Madrigal, Sandra, Ordoñez, Graciela, Guerrero-Camacho, Jorge Luis, Treviño-Frenk, Irene, Escamilla-Tilch, Monica, García-Lechuga, Maricela, Tovar-Méndez, Víctor Hugo, Pacheco-Ubaldo, Hanna, Acuña-Alonzo, Victor, Bortolini, Maria-Cátira, Gallo, Carla, Bedoya, Gabriel, Rothhammer, Francisco, González-Jose, Rolando, Ruiz-Linares, Andrés, Canizales-Quinteros, Samuel, Yunis, Edmond, Granados, Julio, Corona, Teresa
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.08.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 631/250; 692/308; 692/499; Alleles; American Natives - genetics; Aquaporin 4; Aquaporin 4 - genetics; Autoimmune diseases; Case-Control Studies; Disease; DNA microarrays; Drb1 protein; Epidemiology; Female; Gene Frequency; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genetics; Genomes; Histocompatibility antigen HLA; HLA Antigens - genetics; Humanities and Social Sciences; Humans; Laboratories; Male; Mexico - epidemiology; Minority & ethnic groups; multidisciplinary; Multiple sclerosis; Neuromyelitis; Neuromyelitis Optica - epidemiology; Neuromyelitis Optica - genetics; Population; Science; Science (multidisciplinary); Tissue typing; Mexico
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-69224-3

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10 –6 ). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P  = 8 × 10 –10 ). Class II HLA alleles HLA- DQB1 *03:01, - DRB1 *08:02, - DRB1 *16:02, - DRB1 *14:06 and - DQB1 *04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.